Disease relevance of Ubx

• We have purified a member of the Ubx protein family from an overproducing E. coli strain and have shown that it is sequence-specific DNA binding protein [1].
• Here we show that a hybrid version of Ubx (Ubx-VP16), which possesses an enhanced transcriptional activation function, no longer directs A1 denticle pattern in embryonic epidermal cells [2].
• Interactions were confirmed with wild-type Ultrabithorax (UBX) in phage display experiments and by immunoprecipitation for a subset of partners [3].
• In the larval ventral ganglion, Ubx expression is greatest in parasegments 5 and 6, as in the embryonic nervous system [4].
• Using recombinant Sindbis virus, we investigated the function of the homeotic gene Ultrabithorax in the development of butterfly wings and beetle embryos [5].

High impact information on Ubx

• In order to test this hypothesis, we used Dam identification to probe for interactions between the Fab-7 boundary and other regions in the BX-C [6].
• wingless and decapentaplegic signal during endoderm induction in Drosophila to regulate expression of the homeotic gene Ultrabithorax [7].
• Here, we define a minimal wingless response sequence in the midgut enhancer of Ultrabithorax [7].
• In stable transformants, transcriptional stimulation of the Ultrabithorax enhancer by LEF-1 depends on armadillo [7].
• Segmental expression of Hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon exd/pbx [8].

Chemical compound and disease context of Ubx

• We find that after high and persistent levels of Ubx product, the head is replaced by three (C1, C2 and C3) abdominal-like denticle belts [9].

Biological context of Ubx

• We find that whether or not the overexpression of Ubx has a developmental effect on a particular body region of the larva depends on the interactions with the resident homeotic genes [10].
• Normal enhancer function requires positive regulation by Ubx and negative regulation by abd-A [11].
• By generating complementary alterations of the binding sites and the binding specificity of UBX, we show that Ubx directly regulates dpp expression [11].
• In early embryonic development, Ubx expression is controlled by segmentation genes turned on earlier in the developmental hierarchy [12].
• Here, by using classical genetics and double-stranded RNA-mediated gene silencing in the red flour beetle, Tribolium castaneum, a species that develops an appendage on the first abdominal segment, we investigate the roles of Ubx and Abd-A in abdominal limb development [13].

Anatomical context of Ubx

• In a branchiopod crustacean, Ubx/AbdA proteins are expressed in both thorax and abdomen, including the limb primordia, but do not repress limbs [14].
• We conclude that dpp both responds to and regulates Ubx in ps7 of the visceral mesoderm and that Ubx autoregulation within this tissue may be indirect as it requires more components than have previously been thought [15].
• Furthermore, targeted ectopic expression of Ubx or abd-A indicates that these homeotic genes influence muscle cell fates by autonomous action in mesodermal cells [16].
• CONCLUSIONS: The specific requirement for abd-A and not Ubx in gonad development does not reflect differences in the properties of the proteins that these genes encode, but presumably reflects differences in their regulation [17].
• Thus, in contrast to its role in Drosophila segmentation, En does not require the co-factors Exd or Ubx/Abd-A in order to control the synaptic specificity of cockroach sensory neurons [18].

Associations of Ubx with chemical compounds

• The model is also capable of dealing with a complicated genetic situation, a hybrid gene of Ubx and abd-A produced by the C1 deletion [19].
• We have mapped, at high resolution, the distribution of Polycomb protein on the bithorax complex of Drosophila tissue culture cells, using an improved formaldehyde cross-linking and immunoprecipitation technique [20].
• Finally, the steroid hormone ecdysone controls cardiac tube remodelling by impinging on both the regulation of Ubx expression and the modification of AbdA function [21].
• Class I alleles, including Ubl, C4, C11, JH1, and WJK2, enhance Ubx when heterozygous with class II alleles, which include wild-type RpII215 [22].
• Our analyses of mutants that lack the PcG histone methyltransferase (HMTase) E(z) or the trxG HMTase Ash1 provide strong evidence that differential histone lysine trimethylation at the promoter and in the coding region confers transcriptional ON and OFF states of Ubx [23].

Physical interactions of Ubx

• Control of the expression of the bithorax complex genes abdominal-A and abdominal-B by cis-regulatory regions in Drosophila embryos [24].
• The Drosophila bithorax complex Abdominal-B (Abd-B) gene specifies parasegmental identity at the posterior end of the fly [25].
• We find that in the absence of the bithorax complex (BX-C) genes there is Scr expression in the epidermis of the posterior compartments of the thoracic and abdominal parasegments [26].
• The three Hox genes of the Bithorax Complex as well as Antennapedia (Antp) have been shown to be expressed in the posterior cardiac tube, while no Hox gene is expressed in the anterior aorta [27].
• We also provide evidence that Ubx and exd bind to neighboring sites on this DNA and interact directly to stabilize the DNA-bound form of Ubx [28].
• Absence of endogenous Ubx transcription when Ubx levels are highly elevated probably activates Polycomb complexes on a Polycomb response element located in the Ubx major intron [29].

Enzymatic interactions of Ubx

• The Drosophila melanogaster Nipped-B protein facilitates transcriptional activation of the cut and Ultrabithorax genes by remote enhancers [30].

Regulatory relationships of Ubx

• We also show that eve represses expression from the Ubx promoter in Drosophila tissue culture cells, again in a binding site-dependent manner [31].
• We conclude that hb represses Ubx expression directly by binding to BRE and probably other Ubx regulatory elements [12].
• In the abdominal cuticle Scr is prevented from inducing prothoracic structures by the three bithorax complex (BX-C) homeotic genes [32].
• In contrast, abd-A represses Ubx expression in the heart and ectopic overexpression of abd-A transforms aorta cells into heart cardiomyocytes [33].
• Trithorax regulates multiple homeotic genes in the bithorax and Antennapedia complexes and exerts different tissue-specific, parasegment-specific and promoter-specific effects on each [34].

Other interactions of Ubx

• Here we assess the functional significance of some of these interactions by expressing the Antp, Ubx or both homoeotic genes under the control of the heat-shock promoter [35].
• Binding of trithorax and Polycomb proteins to the bithorax complex: dynamic changes during early Drosophila embryogenesis [36].
• In addition, we have identified the minimal fragments from the Ultrabithorax (Ubx) regulatory region that are capable of recruiting TRX to chromosomal sites containing them [36].
• The repressor of the anterior Ubx expression is the gap gene hunchback (hb) [12].
• Footprint analysis and tests in transformed embryos of constructs bearing mutated footprint regions suggest that ftz protein acts directly as a transcriptional activator of Ubx [37].
• We further demonstrate that Ubx executes this role by counteracting the function of Antp in promoting cell survival [38].

Analytical, diagnostic and therapeutic context of Ubx

• There are multiple BX-C elements that mediate Pc group control, which we call Pc group response elements (PREs), and they can work when removed from the normal BX-C context [39].
• Whole mount in situ hybridization of embryos of various ages demonstrates that during early development this gene has temporally and spatially restricted patterns of expression that resemble those of the homoeotic genes of the Drosophila bithorax complex and of many vertebrate homoeobox genes [40].
• In the wild type, the Bithorax Complex forms a weak point featuring thinner bands separated by clefts or constrictions [41].
• In the work reported here we have undertaken a functional dissection of a Polycomb response element (PRE) from the iab-7 cis-regulatory domain of the Drosophila melanogaster bithorax complex (BX-C) [42].
• Coimmunoprecipitations show that ESCL associates with E(Z) in postembryonic cells and chromatin immunoprecipitations show that ESCL tracks closely with E(Z) on Ubx regulatory DNA in wing discs [43].

References